It is established in Japan that treatment with 1alpha-hydroxyvitamin D3 (
alfacalcidol) slightly reduces bone turnover, sustains lumbar bone mineral density (BMD), and prevents osteoporotic vertebral fractures in postmenopausal women with
osteoporosis, while
vitamin K2 (
menatetrenone) enhances gamma-carboxylation of bone
glutamic acid residues and secretion of
osteocalcin, sustains lumbar BMD, and prevents
osteoporotic fractures in patients with
osteoporosis. Available evidence suggests that the effect of
vitamin K2 on mineralization by human periosteal osteoblasts is enhanced in the presence of
1,25 dihydroxyvitamin D3 in vitro. The effect of
vitamin K2 on BMD in ovariectomized rats is affected by the plasma
25-hydroxyvitamin D3 level in vivo, and is significant only when rats are fed a diet containing
vitamin D3. Based on this line of evidence, combined treatment with
alfacalcidol and
menatetrenone for
osteoporosis is surmised to be more effective than treatment with
menatetrenone alone, and may have
anabolic effects on osteoporotic bone. This combined treatment may increase bone formation as well as
bone resorption over the mild anti-resorptive effect of
alfacalcidol itself, and shows the greatest effect on lumbar BMD or the incidence of vertebral fractures in studies in which the mean age and years since menopause of subjects were low and the degree of
osteoporosis was mild. It may be effective for mild
postmenopausal osteoporosis in which age-related deterioration of trabecular bone properties remains below the threshold for vertebral fractures, even if
bone resorption is increased and trabecular bone has deteriorated.